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Abstract Climate mitigation policies have broad environmental and socioeconomic impacts and thus underpin progress towards the United Nations Sustainable Development Goals (SDGs). Through national-scale integrated modeling, we explore the spillover effects of China’s long-term climate mitigation pathways (CMPs) on achieving all 17 SDGs, and then identify a cost-effective CMP for China with co-benefits for sustainability. Our analysis indicates that the 9 original CMPs and 180 bundled CMPs can both substantially boost the SDGs, resulting in an increase of 6.33–8.86 and 5.90–9.33 points in overall SDG score (0=no progress, 100=full achievement) by 2060, compared to the Reference pathway of 70.75 points, respectively. The identified cost-effective CMP deals with the trade-offs among sustainability, CO2 emissions and mitigation cost, and maximizes the synergies between them. This CMP can inform future directions for China’s policy-makers to maximize the potential synergies between carbon neutrality and long-term sustainable development.

Abstract Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.

Abstract Peat moss (Sphagnum) is a non-vascular higher plant with unique xylem-like hyaline (H) cells that are accompanied by photosynthetic chlorophyllous cells. These cellular structures play crucial roles in water storage and carbon sequestration. However, it is largely unknown how peat moss develops the H cells. This study systematically explored the Sphagnum Developmental Cell Atlas and Lineage and classified leaf cell development into two lineages with six stages (S0-S5) based on changes in key cellular traits, including the formation of spiral secondary cell walls (S4) and the presence of water pores (S5). Cell lineage-specific subcellular remodeling was transcriptionally regulated during leaf development, and vacuole-mediated clearance of organelles and cell death led to mature dead H cells. Interestingly, expression of land plant conserved Vascular-related NAC Domain (VND) genes correlated with H cell formation. Overall, these results suggest that the origination of xylem-like H cells is related to VND, likely through the neofunctionalization of vacuole-mediated cell death to attempt xylem formation in peat moss, suggesting potential uncoupling of xylem and phloem cell origins. This study positions peat moss as a potential model organism for studying integrative evolutionary cell biology.

Abstract Necrotizing fasciitis (NF) is a rare and life-threatening serious infectious disease, characterized by acute onset and rapid progress, leading to extensive necrosis of skin, soft tissue as well as fascia by a variety of aerobic and anaerobic bacteria, localized on external genitalia, scrotum, groin and perianal areas in males. There exist numerous common etiologies for NF, yet NF induced by malignant neoplasms is exceedingly rare. Several studies have reported that NF may be associated with tumor site (rectal/sigmoid colon cancer) and blood supply dysfunction caused by targeted therapy drugs (bevacizumab, aflibercept, ramucirumab). The perforation of colorectal cancer poses a unique risk factor for NF. However, in our two cases, the patient with rectal cancer received CapeOX (oxaliplatin + capecitabine) + bevacizumab + tislelizumab for 3 cycles without perforation but did develop NF. One month after debridement, the patient continued immunotherapy with tislelizumab alone for the fourth cycle and maintained for an additional 3 cycles without any recurrence of NF. Therefore, does the occurrence of NF correlate with the tumor site (rectum) and targeted immunotherapy? Another patient with hepatocellular carcinoma also developed NF after receiving 2 cycles of lenvatinib + sintilimab treatment. The third cycle of sintilimab immunotherapy was administered on the 13th day after operation, which was subsequently maintained for an additional 2 cycles without recurrence of NF. The absence of a direct correlation between hepatocellular carcinoma and rectal tumor location as well as immunotherapy, suggests that NF may be closely linked to targeted therapy.

Abstract The norovirus (NoV) genome is diverse. Therefore, this study explored the epidemiological characteristics and genetic features of NoV in Ningxia Hui Autonomous Region, China, from 2011 to 2022 to clarify the genetic diversity in this region. Stool samples were screened for NoV and then sequenced and genotyped. In total, 1,788 of 13,083 specimens were NoV -positive (13.67%); 204 (1.56%) and 1,584 (12.11%) cases were GI and GII, respectively. Additionally, 559 were NoV infection with other viruses (4.27%), primarily with rotavirus (277/559, 49.55%). The NoV incidence rate was the highest among children aged 0–2 years (18.09%, 1054/5,828) and lowest among adults aged 45–64 years (110/1,495, 7.36%); it was also higher in the winter and spring than in the other seasons. GI.3[P3] was the dominant GI genotype. The dominant GII genotype changed roughly every two years. In the GII group, GII.4 was the most common genotype (46.79%), followed by GII.3 (21.34%), GII.2 (12.34%), and GII.17 (9.77%). There were three variants of GII.4 Den Haag, GII.4 New Orleans and GII.4 Sydney identified in the detected GII.4 strains, with GII.4 Sydney dominating. The GII.4 (87.36%), GII.3 (86.35%), and GII.2 (72.92%) strains were primarily detected in children, whereas it was the GII.17 (52.63%) strain in adults. Overall, the NoV genotypes in the Ningxia Hui Autonomous Region were diverse. Primarily, GII groups were dominant, but this changed over time.

Abstract Currently, the relationship between axial rotation of the vertebrae and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) remains controversial. The aim of this study is to quantitatively assess the effect of vertebral rotation on volumetric bone mineral density (v-BMD) and areal bone mineral density (a-BMD), further to propose the corrected strategies. To achieve this, a phantom, which was rotated from 0° to 25° in 5° increments, was utilized. Bone mineral content (BMC), a-BMD, v-BMD, and projected area (p-AREA) were measured. The Kruskal–Wallis non-parametric test or one-way ANOVA was used to examine the differences in variables between the different groups. The Pearson and Spearman correlation was used to test the relationships between quantitative parameters and rotated angles. Linear regression analysis was used to evaluate the relationship between angles and quantitative parameters. The findings indicate that, as the angle increased, a-BMD and v-BMD decreased (P

The Yangtze River is the mother river of China. To promote the aquatic ecosystem protection of the great river, the Project of Yangtze Fisheries Resources and Environment Investigation (2017–2021) supported by the Ministry of Agriculture and Rural Affairs, P. R. China carried out by 24 institutes and universities that located in the Yangtze River basin surveys the status of (1) fish species composition and spatial distribution, (2) current fish abundance, (3) endangered fishes, (4) Yangtze finless porpoise, (5) aquatic eco-environments, (6) water-level fluctuation areas, (7) capture fisheries and recreational fisheries of the Yangtze River mainstream and 10 of its main tributaries, including Yalong River, Heng River, Min River (including Dadu River), Chishui River, Tuo River, Jialing River, Wu River, Han River, Dongting Lake and Poyang Lake. The results showed that there were 443 fish species (belonging to 163 genus, 37 families, and 18 orders) before 2017, but only 323 fish species (including 15 new recorded exotic species) were recorded in the project of 2017–2021. Among them, Cyprinus carpio, Carassius auratus, Hypophthalmichthys molitrix, Pelteobagrus fulvidraco, Coilia brachygnathus, Silurus asotus, Saurogobio dabryi, Ctenopharyngodon idellus, Pelteobagrus nitidus, Hemiculter leucisculus, Siniperca chuatsi, Coreius heterodon, Culter alburnus, Parabramis pekinensis, and Aristichthys nobilis were the dominant species across the whole Yangtze River system. It is estimated that there were 886 million individuals weighing 124.8 million kg, merely equivalent to 27.3% of the resources in 1950s, 30.9% of the resources in 1960s, or 58.7% of the resources in 1980s. In the new list of protected fishes that recorded in the Yangtze River system, only 15 of 29 were collected in this project of 2017–2021. Psephurus gladius has been affirmed to be Extinct by International Union for Conservation of Nature (IUCN). The wild individuals of Tenualosa reevesii and Luciobrama macrocephalus have disappeared for many years and maybe have been extinct already. Acipenser dabryanus has been affirmed to be Extinct in the Wild by IUCN. The natural propagations of A. sinensis, Myxocyprinus asiaticus and Trachidermus fasciatus have been interrupted for many years. The populations of Yangtze finless porpoise in the Yangtze River mainstream, Dongting Lake and Poyang Lake have steadily rising sizes and expanding distributions in 2017–2021. Parts of them migrate from one region to another with the seasons, which would result in the fluctuation of Yangtze finless porpoise population within some regions. The conventional indicators of water quality in the Yangtze River system were good and conformed to the water quality criteria of fishery in 2017–2021. In the last 40 years, the maximum surface water area in the Yangtze River basin extended to approximately 63,360 km2, the minimum surface water area covered approximately 26,396 km2, and the seasonal water-level fluctuation areas occupied approximately 36,964 km2. Compared with 1984–2000 period, the 2001–2020 period witnessed an overall decreasing trend in the frequency of surface water occurrence within about 25,869 km2 of aquatic areas. From 1984 to 2000 period to 2001–2020 period, permanent surface water has decreased by nearly 8,750 km2. In 2017, the fishermen were mainly 40–60 years old and their educational levels were mainly lower than junior high school. In 2017, most anglers were older than 40 and used hand rod and/or sea rod. Their average catch of each time was mainly less than 1 kg. Results suggested that the fishing ban in key waters of the Yangtze River basin is not only an ecological project of aquatic ecosystem conservation, but also a livelihood project for the fisherman to embrace industrial transformation and improve their living conditions. After the implementation of the fishing ban, the fisheries resources would gradually recover, and the Yangtze finless porpoise population size would also see a steady increase. However, the endangered species would remain threatened for a long time. The degraded waterbodies and water-level fluctuation areas would be the key restrictive factors for future aquatic ecosystem recovery in the Yangtze River basin. Since this survey was carried out before the fishing ban, the current results could provide a baseline for future evaluation of the effect of the Yangtze River fishing ban.

Abstract Enhanced recovery after surgery (ERAS) has been successfully integrated into a diverse array of surgical fields to improve the quality and efficacy of treatment intervention. Nonetheless, the application of the ERAS protocol for patients with diabetic foot ulcer (DFU) subsequent to undergoing surgical procedures has not been previously explored. Therefore, this study aimed to investigate the effect of an enhanced recovery protocol on perioperative outcomes in patients with DFU following surgical procedures. A retrospective analysis was conducted on 112 patients with DFU who underwent surgery between January 2020 and December 2021 at a tertiary referral care center. In total, 57 patients received standard perioperative care (the non-ERAS group), and 55 patients received ERAS care (the ERAS group). The primary outcomes included the length of stay (LOS), wound healing time, patient satisfaction, and costs, serving as the basis for assessing the effectiveness of the two approaches. Secondary outcomes included preoperative anxiety (APAIS score), nutritional status (PG-SGA), pain (NRS score), the incidence of lower-extremity deep vein thrombosis (DVT), the reduction in lower-limb circumference, and the activity of daily living scale (Barthel Index). The ERAS group exhibited significantly shorter LOS (11.36 vs. 26.74 days; P 0.05). By reducing the LOS and hospital costs, and by minimizing perioperative complications, the ERAS protocol improves the quality and efficacy of treatment intervention in patients with DFU who underwent surgical procedures. Trial registration number: ChiCTR 2200064223 (Registration Date: 30/09/2022).

Few existing research examines the relationship between transformational leadership and professional learning communities. This study aims to explore the relationship between transformational leadership and professional learning community components from the perspective of teachers in the Chinese context. A total of 385 primary school teachers participated in the questionnaire survey. This quantitative study used the 12-item Multifactor Leadership Questionnaire and the16-item PLC scale. The structural equation model showed a good fit. The results showed that transformational leadership had a significant positive effect on professional learning community. Moreover, it has a significant impact on all four components of PLC, namely, organizational learning, shared responsibility, reflective dialogue, de-privatized practice. Transformational leadership conflicts with Chinese Confucian culture on some core features, which provides valuable cases for research on the applicability of transformational leadership in different contexts. At the same time, it also provides empirical evidence for the study of the relationship between transformational leadership and professional learning communities.

Abstract Rationale and objective To investigate the impact of the contrast enhancement boost (CE-boost) technique on the image quality of CT angiography (CTA) derived from 80-kVp cerebral CT perfusion (CTP) data, and to compare it with conventional CTApeak as well as other currently employed methods for enhancing CTA images, such as CTAtMIP and CTAtAve extracted from CTP. Materials and methods The data of forty-seven patients who underwent CTP at 80 kVp were retrospectively collected. Four sets of images: CTApeak, CTAtMIP, CTAtAve, and CE-boost images. The CTApeak image represents the arterial phase at its peak value, captured as a single time point. CTAtMIP and CTAtAve are 4D CTA images that provide maximum density projection and average images from the three most prominent time points. CE-boost is a postprocessing technique used to enhance contrast in the arterial phase at its peak value. We compared the average CT value, standard deviation (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the internal carotid artery (ICA) and basilar artery (BA) among the four groups. Image quality was evaluated using a 5-point scale. Results The CE-boost demonstrated and CNR in the ICA and BA (all p

Abstract Esophageal cancer, ranked as the seventh most common cancer globally, encompasses squamous cell carcinoma and adenocarcinoma. Despite advancements in treatment modalities like surgery, chemotherapy, radiotherapy, and immunotherapy, radiotherapy, while crucial for enhancing local control and survival, poses risks for long-term side effects and the development of second primary malignancies (SPM), notably Second primary lung cancer (SPLC). This study aims to analyze the incidence of second primary lung cancer (SPLC) among esophageal cancer survivors, with a focus on the influence of radiotherapy, analyze variations across different demographic and clinical subgroups, and assess patient survival outcomes. Using data from the Surveillance, epidemiology, and end results (SEER) program on 56,493 esophageal cancer patients (2000–2020), we compared SPLC incidence in those with and without prior radiotherapy. We applied a competing risks framework, propensity score matching (PSM), and survival analyses to assess SPLC risk and radiotherapy’s impact. The study showed that patients treated with radiotherapy have a significantly higher long-term risk of SPLC compared to those without it. Radiotherapy significantly raised SPLC risk (HR 1.41, 95% CI 1.06–1.88), with higher SIRs particularly in younger patients and females. Post-PSM, there were significant differences in cancer-specific survival between esophageal cancer survivors with post-radiotherapy SPLC and those with only primary lung cancer. This cohort study shows that radiotherapy in esophageal cancer survivors increases SPLC risk but does not worsen survival compared to those with OPLC, highlighting the need for long-term monitoring and management.

Abstract The redox state of arc mantle has been considered to be more oxidized and diverse than that of the mid-ocean ridge, but the cause of the variation is debated. We examine the redox state of the Cenozoic global arc mantle by compiling measured/calculated fO2 of olivine-hosted melt inclusions from arc magma and modeled fO2 based on V/Sc and Cu/Zr ratios of arc basaltic rocks. The results indicate that the redox state of Cenozoic arc mantle is latitude dependent, with less oxidized arc mantle in the low latitudes, contrasting with a near constant across-latitude trend in the mid-ocean ridges. We propose that such a latitude-dependent pattern in the arc mantle may be controlled by the variation in the redox state of subducted sediment, possibly related to a latitudinal variation in the primary production of phytoplankton, which results in more organic carbon and sulfide deposited on the low-latitude ocean floor. Our findings provide evidence for the impact of the surface environment on Earth’s upper mantle.

Objective: To create a nomogram-based model to estimate the Chinese population's 5-year risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: We randomly divided 7582 participants into two groups in a 7:3 ratio: one group was assigned to work with the training set, which consisted of 5307 cases, and the other group was assigned to validate the model using 2275 cases. The least absolute shrinkage and selection operator model was employed to ascertain the variables with the highest correlation among all potential variables. A logistic model was constructed by incorporating these selected variables, which were subsequently visualized using a nomogram. The discriminatory ability, calibration, and clinical utility of the model were assessed using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: During the 5-year follow-up, 1034 (13.64%) total participants were newly diagnosed with MASLD. Using eight variables (gender, body mass index, waist, hemoglobin, alanine aminotransferase, uric acid, triglycerides, and high-density lipoprotein), we built a 5-year MASLD risk prediction model. The nomogram showed an area under the ROC of 0.795 (95% CI: 0.779–0.811) in the training set and 0.785 (95% CI: 0.760–0.810) in the validation set. The calibration curves revealed a 5-year period of agreement between the observed and predicted MASLD risks. DCA curves illustrated the practicality of this nomogram over threshold probability profiles ranging from 5% to 50%. Conclusion: We created and tested a nomogram to forecast the risk of MASLD prevalence over the next 5 years.

Abstract Direct reduction of unactivated alkyl halides for C(sp3)-N couplings under mild conditions presents a significant challenge in organic synthesis due to their low reduction potential. Herein, we introduce an in situ formed pyridyl-carbene-ligated copper (I) catalyst that is capable of abstracting halide atom and generating alkyl radicals for general C(sp3)-N couplings under visible light. Control experiments confirmed that the mono-pyridyl-carbene-ligated copper complex is the active species responsible for catalysis. Mechanistic investigations using transient absorption spectroscopy across multiple decades of timescales revealed ultrafast intersystem crossing (260 ps) of the photoexcited copper (I) complexes into their long-lived triplet excited states (>2 μs). The non-Stern-Volmer quenching dynamics of the triplets by unactivated alkyl halides suggests an association between copper (I) complexes and alkyl halides, thereby facilitating the abstraction of halide atoms via inner-sphere single electron transfer (SET), rather than outer-sphere SET, for the formation of alkyl radicals for subsequent cross couplings.

Abstract Background The Atribacterota are widely distributed in the subsurface biosphere. Recently, the first Atribacterota isolate was described and the number of Atribacterota genome sequences retrieved from environmental samples has increased significantly; however, their diversity, physiology, ecology, and evolution remain poorly understood. Results We report the isolation of the second member of Atribacterota, Thermatribacter velox gen. nov., sp. nov., within a new family Thermatribacteraceae fam. nov., and the short-term laboratory cultivation of a member of the JS1 lineage, Phoenicimicrobium oleiphilum HX-OS.bin.34TS, both from a terrestrial oil reservoir. Physiological and metatranscriptomics analyses showed that Thermatribacter velox B11T and Phoenicimicrobium oleiphilum HX-OS.bin.34TS ferment sugars and n-alkanes, respectively, producing H2, CO2, and acetate as common products. Comparative genomics showed that all members of the Atribacterota lack a complete Wood-Ljungdahl Pathway (WLP), but that the Reductive Glycine Pathway (RGP) is widespread, indicating that the RGP, rather than WLP, is a central hub in Atribacterota metabolism. Ancestral character state reconstructions and phylogenetic analyses showed that key genes encoding the RGP (fdhA, fhs, folD, glyA, gcvT, gcvPAB, pdhD) and other central functions were gained independently in the two classes, Atribacteria (OP9) and Phoenicimicrobiia (JS1), after which they were inherited vertically; these genes included fumarate-adding enzymes (faeA; Phoenicimicrobiia only), the CODH/ACS complex (acsABCDE), and diverse hydrogenases (NiFe group 3b, 4b and FeFe group A3, C). Finally, we present genome-resolved community metabolic models showing the central roles of Atribacteria (OP9) and Phoenicimicrobiia (JS1) in acetate- and hydrocarbon-rich environments. Conclusion Our findings expand the knowledge of the diversity, physiology, ecology, and evolution of the phylum Atribacterota. This study is a starting point for promoting more incisive studies of their syntrophic biology and may guide the rational design of strategies to cultivate them in the laboratory. Video Abstract

Abstract China’s long-term sustainability faces socioeconomic and environmental uncertainties. We identify five key systemic risk drivers, called disruptors, which could push China into a polycrisis: pandemic disease, ageing and shrinking population, deglobalization, climate change, and biodiversity loss. Using an integrated simulation model, we quantify the effects of these disruptors on the country’s long-term sustainability framed by 17 Sustainable Development Goals (SDGs). Here we show that ageing and shrinking population, and climate change would be the two most influential disruptors on China’s long-term sustainability. The compound effects of all disruptors could result in up to 2.1 and 7.0 points decline in the China’s SDG score by 2030 and 2050, compared to the baseline with no disruptors and no additional sustainability policies. However, an integrated policy portfolio involving investment in education, healthcare, energy transition, water-use efficiency, ecological conservation and restoration could promote resilience against the compound effects and significantly improve China’s long-term sustainability.

Abstract Intestinal fibrosis is a prevalent complication of IBD that that can frequently be triggered by prolonged inflammation. Fibrosis in the gut can cause a number of issues, which continue as an ongoing challenge to healthcare systems worldwide. The primary causes of intestinal fibrosis are soluble molecules, G protein-coupled receptors, epithelial-to-mesenchymal or endothelial-to-mesenchymal transition, and the gut microbiota. Fresh perspectives coming from in vivo and in vitro experimental models demonstrate that fibrogenic pathways might be different, at least to some extent, independent of the ones that influence inflammation. Understanding the distinctive procedures of intestinal fibrogenesis should provide a realistic foundation for targeting and blocking specific fibrogenic pathways, estimating the risk of fibrotic consequences, detecting early fibrotic alterations, and eventually allowing therapy development. Here, we first summarize the inflammatory and non-inflammatory components of fibrosis, and then we elaborate on the underlying mechanism associated with multiple cytokines in fibrosis, providing the framework for future clinical practice. Following that, we discuss the relationship between modernization and disease, as well as the shortcomings of current studies. We outline fibrosis diagnosis and therapy, as well as our recommendations for the future treatment of intestinal fibrosis. We anticipate that the global review will provides a wealth of fresh knowledge and suggestions for future fibrosis clinical practice. Graphical Abstract

Abstract Background The proliferation of porcine ovarian granulosa cells (GCs) is essential to follicular development and the ubiquitin–proteasome system is necessary for maintaining cell cycle homeostasis. Previous studies found that the deubiquitinase ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) regulates female reproduction, especially in ovarian development. However, the mechanism by which UCHL1 regulates porcine GC proliferation remains unclear. Results UCHL1 overexpression promoted GC proliferation, and knockdown had the opposite effect. UCHL1 is directly bound to cyclin B1 (CCNB1), prolonging the half-life of CCNB1 and inhibiting its degradation, thereby promoting GC proliferation. What’s more, a flavonoid compound-isovitexin improved the enzyme activity of UCHL1 and promoted the proliferation of porcine GCs. Conclusions UCHL1 promoted the proliferation of porcine GCs by stabilizing CCNB1, and isovitexin enhanced the enzyme activity of UCHL1. These findings reveal the role of UCHL1 and the potential of isovitexin in regulating proliferation and provide insights into identifying molecular markers and nutrients that affect follicle development.

Abstract Background To investigate the changes in the unhealthy eye-related behaviors of junior middle school students during the COVID-19 pandemic and the double reduction policy and its relationship with myopia. Methods Data were obtained from the 2019–2022 Tianjin Children and Youth Myopia, Common Diseases and Health Influencing Factors Survey. Latent profile analysis (LPA) and a generalized linear model (GLM) were applied to analyze the effect of eye-related behavior classes on myopia. Results A total of 2508 junior middle school students were included. The types of eye-related behavior were categorized into the medium-healthy behavior group, heavy academic burden and near-eye behavior group, insufficient lighting group and high-healthy behavior group. Students with heavy academic burdens and near-eye behavior were more likely to develop myopia than were those in the high-healthy group (OR = 1.466, 95% CI = 1.203–1.787; P

Background The evidence for optical coherence tomography (OCT)–guided percutaneous coronary intervention (PCI) in improving the prognosis of individuals with in‐stent restenosis (ISR) is lacking. Methods and Results This retrospective study enrolled 588 consecutive individuals with drug‐eluting stent ISR undergoing PCI from March 2010 to March 2022. Two hundred seven (35.2%) underwent OCT guidance, and 381 (64.8%) underwent angiography guidance. Clinical outcomes were analyzed using survival curves. The primary clinical endpoint was 2‐year major adverse cardiovascular events (MACEs), a composite of all‐cause death, myocardial infarction, and target‐vessel revascularization. Compared with angiography guidance, OCT guidance demonstrated a higher frequency of drug‐coated balloon use and adjunctive therapeutic modalities, including predilation, postdilation, nonslip element balloons, and noncompliant balloons (P

Stimulator of interferon genes (STING) has recently been found to play a crucial role in cardiac sterile inflammation and dysfunction. The role of stimulator of interferon genes (STING) in cardiac sterile inflammation and dysfunction has been recently discovered. This study aims to examine the involvement of STING in pathological cardiac remodeling and the mechanisms that govern the activation of the STING pathway. To investigate this, transverse aortic constriction (TAC) was performed on STING knockout mice to induce pressure overload-induced cardiac remodeling. Subsequently, cardiac function, remodeling, and inflammation levels were evaluated. The STING pathway was found to be activated in the pressure overload-stressed heart and angiotensin II (Ang II)-stimulated cardiac fibroblasts. Loss of STING expression led to a significant reduction in inflammatory responses, mitochondrial fragmentation, and oxidative stress in the heart, resulting in attenuated cardiac remodeling and dysfunction. Furthermore, the exacerbation of pressure overload-induced STING-mediated inflammation and pathological cardiac remodeling was observed when mitophagy was suppressed through the silencing of Parkin, an E3 ubiquitin ligase. Taken together, these findings indicate that STING represents a newly identified and significant molecule implicated in the process of pathological cardiac remodeling and that mitophagy is an upstream mechanism that regulates STING activation. Targeting STING may therefore provide a novel therapeutic strategy for pathological cardiac remodeling and heart failure.

The kiwifruit canker disease caused by Pseudomonas syringae pv. actinidiae (Psa) seriously threatens the development of kiwifruit industry. So far, only a limited number of Psa-resistant kiwifruit varieties have been identified, and the underlying molecular mechanisms are still largely unknown. In this study, we evaluated the Psa resistance of six hybrid populations and screened a resistant segregation population R1F2. Then, transcriptome analysis on the Psa extremely high-resistant (HR) and extremely high-susceptible (HS) plants of the R1F2 population was performed. KEGG enrichment analysis revealed that differentially expressed genes (DEGs) were significantly enriched in plant hormone signal transduction pathways, including auxin, abscisic acid, zeatin, jasmonic acid and salicylic acid. Furthermore, several transcription factors (TFs), especially WRKY TFs, were identified among the DEGs. The qRT-PCR showed that AcWRKY75 was highly expressed in the HS plants. Additionally, AcWRKY75 was significantly induced in the HS cultivar ‘Hongyang’ after Psa inoculation. Sequence amplification analysis showed that there was polymorphism in the DNA sequence of AcWRKY75 gene, but no HR or HS-specific differences were observed. Subcellular localization and transcriptional activity analysis confirmed that AcWRKY75 functions as a nucleus-located transcriptional activator. Transient overexpression of AcWRKY75 in kiwifruit leaves reduced the resistance to Psa, while silencing AcWRKY75 by virus-induced gene silencing (VIGS) slightly enhanced the resistance to Psa. Furthermore, AcWRKY75 exhibited a weak interaction with the promoter of the ABA-related DEG AcBet V1 (Acc27163). Our findings elucidated that AcWRKY75 may negatively regulate the Psa resistance of kiwifruit through the hormone signaling pathway, which laid a foundation for the analysis of the disease resistance mechanism of kiwifruit canker.

Abstract Magnetron‐sputtered thermoelectric thin films have the potential for reproducibility and scalability. However, lattice mismatch during sputtering can lead to increased defects in the epitaxial layer, which poses a significant challenge to improving their thermoelectric performance. In this work, nanocrystalline n‐type Bi2Te3 thin films with an average grain size of ≈110 nm are prepared using high‐temperature sputtering and post‐annealing. Herein, it is demonstrated that high‐temperature treatment exacerbates Te evaporation, creating Te vacancies and electron‐like effects. Annealing improves crystallinity, increases grain size, and reduces defects, which significantly increases carrier mobility. Furthermore, the pre‐deposited Ti additives are ionized at high temperatures and partially diffused into Bi2Te3, resulting in a Ti doping effect that increases the carrier concentration. Overall, the 1 µm thick n‐type Bi2Te3 thin film exhibits a room temperature resistivity as low as 3.56 × 10−6 Ω∙m. Notably, a 5 µm thick Bi2Te3 thin film achieves a record power factor of 6.66 mW mK−2 at room temperature, which is the highest value reported to date for n‐type Bi2Te3 thin films using magnetron sputtering. This work demonstrates the potential for large‐scale of high‐quality Bi2Te3‐based thin films and devices for room‐temperature TE applications.

Acute leukemia (AL) is a rare yet perilous malignancy. Currently, the primary treatment for AL involves combination chemotherapy as the cornerstone of comprehensive measures, alongside hematopoietic stem cell transplantation as a radical approach. However, despite these interventions, mortality rates remain high, particularly among refractory/recurrent patients or elderly individuals with a poor prognosis. Acetylation, a form of epigenetic regulation, has emerged as a promising therapeutic avenue for treating AL. Recent studies have highlighted the potential of acetylation regulation as a novel treatment pathway. Histone deacetylase inhibitors (HDACis) play a pivotal role in modulating the differentiation and development of tumor cells through diverse pathways, simultaneously impacting the maturation and function of lymphocytes. HDACis demonstrate promise in enhancing survival rates and achieving a complete response in both acute myeloid leukemia and acute T-lymphoblastic leukemia patients. This article provides a comprehensive review of the advancements in HDACi therapy for AL, shedding light on its potential implications for clinical practice.

Abstract Realizing transformation from transparent insulating to transparent conducting, is a pursuing goal in designing and fabricating novel optoelectronic materials and devices. Here, a pronounced insulating to metal transition in anatase TiO2 thin films is achieved through ionic liquid gating, and interestingly the material maintains an invariable high optical transparency. It is revealed that the emergent metallic state can be attributed to the electron doping associated with the hydrogen ion intercalation. Importantly, the hydrogenation leads to the almost rigid shift of the Fermi energy and therefore maintains nicely the transparency at the visible light region. This result is in strong contrast with the case of oxygen vacancy doping, in which the optical bandgap is suppressed due to improved orbitals hybridization and intraband transition. Moreover, through synergistic ion‐electron doping, the selective control of the gating area and pattern is realized in the micrometer or even nanometer scale with extremely distinct physical properties, which can be employed to fabricate novel optical and electronic devices. The result greatly deepens the understanding of the underlying physics and formation mechanism of transparent conducting oxide (TCO) materials. It is envisioned that this work would provide a new pathway to design other potential optoelectronic materials with novel functionalities.

Stock market is a complex system characterized by collective activity, where interdependencies between stocks have a significant influence on stock price trends. It is widely believed that modeling these dependencies can improve the accuracy of stock trend prediction and enable investors to earn more stable profits. However, these dependencies are not directly observable and need to be analyzed from stock data. In this paper, we propose a model based on Long short-term memory (LSTM) and graph convolutional network to capture these dependencies for stock trend prediction. Specifically, an LSTM is employed to extract the stock features, with all hidden state outputs utilized to construct the graph nodes. Subsequently, Pearson correlation coefficient is used to organize the stock features into a graph structure. Finally, a graph convolutional network is applied to extract the relevant features for accurate stock trend prediction. Experiments based on China A50 stocks demonstrate that our proposed model outperforms baseline methods in terms of prediction performance and trading backtest returns. In trading backtest, we have identified a set of effective trading strategies as part of the trading plan. Based on China A50 stocks, our proposed model shows promising results in generating desirable returns during both upward and downward channels of the stock market. The proposed model has proven beneficial for investors to seeking optimal timing and pricing when dealing with shares.

Background Many disease processes are influenced by circadian clocks and display ~24‐hour rhythms. Whether disruptions to these rhythms increase stroke risk is unclear. We evaluated the association between 24‐hour rest‐activity rhythms, stroke risk, and major poststroke adverse outcomes. Methods and Results We examined ~100 000 participants from the UK Biobank (aged 44–79 years; ~57% women) assessed with actigraphy (6–7 days) and 5‐year median follow‐up. We derived (1) most active 10‐hour activity counts across the 24‐hour cycle and the timing of its midpoint timing; (2) the least active 5‐hour count and its midpoint; (3) relative amplitude; (4) interdaily stability; and (5) intradaily variability, for stability and fragmentation of the rhythm. Cox proportional hazard models were constructed for time to (1) incident stroke (n=1652) and (2) poststroke adverse outcomes (dementia, depression, disability, or death). Suppressed relative amplitude (lowest quartile [quartile 1] versus the top quartile [quartile 4]) was associated with stroke risk (hazard ratio [HR], 1.61 [95% CI, 1.35–1.92]; P

The incidence of colorectal cancer is relatively high in our country, with the majority of patients being diagnosed at an advanced stage. For individuals with advanced-stage colorectal cancer, conversion or neoadjuvant therapy is frequently necessitated to facilitate surgical intervention and achieve a curative effect. And about 10% to 30% of colon cancer patients are complicated with intestinal obstruction. Surgical intervention remains the primary treatment for managing intestinal obstructions, albeit with a considerable risk of perioperative mortality and an increased likelihood of postoperative complications. PDT, as a neoadjuvant treatment for colon cancer, can shrink the local tumor and relieve obstruction, and is effective in colon cancer combined with obstruction. Robotic surgery has the advantages of high stability and low trauma, and compared with laparoscopic colon cancer surgery, robotic surgery can achieve better results. Fluorescent laparoscopic clarifies the location and size of the tumor lesion, allowing for greater precision when removing colon cancer lesions in robotic surgery. Therefore, in the treatment of colon cancer, PDT can offer an opportunity for surgery after relieving obstruction in patients with obstructive colon cancer. Additionally, when combined with fluorescent laparoscopic robotic colon cancer surgery, it provides a novel treatment approach for patients with obstructive colon cancer. Preoperative photodynamic neoadjuvant therapy combined with robotic colon cancer surgery has not yet been reported. Here, we report a case of colon cancer with obstruction, preoperative TNM stage was T4N1, and the lesion had caused intestinal stenosis. After four sessions of PDT, the patient’s intestinal lumen was unobstructed and the lesion had regressed. After evaluation, fluorescent laparoscopic localization and visualization of lymph nodes combined with robotic colon cancer resection were performed. Postoperative pathology showed that the patient’s tumor regression grade was grade 1. The patient’s tumor was completely resected with good resection effect. No tumor invasion was found on both sides of the resection margin, and the patient did not relapse after surgery.

Sample collection and measurement of soil bulk density (BD) are often labor-intensive and expensive in large regions. Conversely, soil spectra are easy to measure and facilitate BD prediction. However, the literature suggests that the damage to the physical structure of soil during scanning spectra on the ground and/or sieved samples might hinder the capacity of spectral technology to accurately predict BD. In addition, because some soil properties that have high correlations with BD, such as the soil organic matter (SOM), are routinely measured and available in most soil databases, coupling them with soil spectra may improve BD prediction compared to using soil properties or spectra. Therefore, in this study, we propose a novel spectral pedo-transfer function (spectral PTF) that couples the measured visible and near-infrared spectra of soils on intact samples and other soil properties to accurately predict the BD (BD = f (soil spectra, soil properties)), which is different from the traditional PTF that uses only soil properties (BD = f (soil properties)) or spectra alone (BD = f (soil spectra)). In this study, we collected topsoil (0–20 cm) and subsoil (20–40 cm) samples from 586 sites in Northeast China, covering a large area of 1.09 million km2 characterized by black soils with high SOM contents. Five routinely measured soil properties were selected: SOM, moisture content (MC), Sand, Silt, and Clay, and various spectral PTFs with one, two, and three soil properties were calibrated using the partial least square regression. The cross-validation results show that the traditional PTF can only predict BD for subsoil with an R2 of 0.51 and an RMSE of 0.11 g·cm−3 when using SOM + MC + Silt or SOM + MC. Compared to subsoil, topsoil and all layers (topsoil + subsoil) had a lower BD prediction accuracy, and a saturation effect was observed for BD values above 1.5 g·cm−3. Unexpectedly, the soil spectra did not provide a higher BD prediction accuracy than traditional PTFs, although the spectra were measured on intact samples. However, adding soil properties to the spectral PTF improved the prediction accuracy and saturation effect for high BD values. The optimal spectral PTF with a single soil property (MC) showed an acceptable BD prediction performance with R2≥0.49, RPD>1.4, and RPIQ>1.7 regardless of whether the sample was topsoil, subsoil, or all layers. Furthermore, the spectral PTF with two or three soil properties yielded a slightly better prediction performance and a more stable prediction among different combinations of soil properties. These results indicate that soil properties and spectra are irreplaceable for BD prediction. Our study demonstrates the potential of spectral PTFs for the accurate prediction of BD and offers insights into the prediction of other soil properties using soil spectra.

Abstract Background Patient safety culture is an integral part of healthcare delivery both in Ghana and globally. Therefore, understanding how frontline health workers perceive patient safety culture and the factors that influence it is very important. This qualitative study examined the health workers’ perceptions of patient safety culture in selected regional hospitals in Ghana. Objective This study aimed to provide a voice concerning how frontline health workers perceive patient safety culture and explain the major barriers in ensuring it. Method In-depth semi-structured interviews were conducted with 42 health professionals in two regional government hospitals in Ghana from March to June 2022. Participants were purposively selected and included medical doctors, nurses, pharmacists, administrators, and clinical service staff members. The inclusion criteria were one or more years of clinical experience. Interviews were recorded and transcribed. Thematic analysis was used to identify themes. Result The health professionals interviewed were 38% male and 62% female, of whom 54% were nurses, 4% were midwives, 28% were medical doctors; lab technicians, pharmacists, and human resources workers represented 2% each; and 4% were critical health nurses. Among them, 64% held a diploma and 36% held a degree or above. This study identified four main areas: general knowledge of patient safety culture, guidelines and procedures, attitudes of frontline health workers, and upgrading patient safety culture. Conclusions This qualitative study presents a few areas for improvement in patient safety culture. Despite their positive attitudes and knowledge of patient safety, healthcare workers expressed concerns about the implementation of patient safety policies outlined by hospitals. Healthcare professionals perceived that curriculum training on patient safety during school education and the availability of dedicated officers for patient safety at their facilities may help improve patient safety.

Abstract Goats have achieved global prominence as essential livestock since their initial domestication, primarily owing to their remarkable adaptability to diverse environmental and production systems. Differential selection pressures influenced by climate have led to variations in their physical attributes, leaving genetic imprints within the genomes of goat breeds raised in diverse agroecological settings. In light of this, our study pursued a comprehensive analysis, merging environmental data with single nucleotide polymorphism (SNP) variations, to unearth indications of selection shaped by climate-mediated forces in goats. Through the examination of 43,300 SNPs from 51 indigenous goat breeds adapting to different climatic conditions using four analytical methods: latent factor mixed models (LFMM), F-statistics (Fst), Extended haplotype homozygosity across populations (XPEHH), and spatial analysis method (SAM), A total of 74 genes were revealed to display clear signs of selection, which are believed to be influenced by climatic conditions. Among these genes, 32 were consistently identified by at least two of the applied methods, and three genes (DENND1A, PLCB1, and ITPR2) were confirmed by all four approaches. Moreover, our investigation yielded 148 Gene Ontology (GO) terms based on these 74 genes, underlining pivotal biological pathways crucial for environmental adaptation. These pathways encompass functions like vascular smooth muscle contraction, cellular response to heat, GTPase regulator activity, rhythmic processes, and responses to temperature stimuli. Of significance, GO terms about endocrine regulation and energy metabolic responses, key for local adaptation were also uncovered, including biological processes, such as cell differentiation, regulation of peptide hormone secretion, and lipid metabolism. These findings contribute to our knowledge of the genetic structure of climate-triggered adaptation across the goat genome and have practical implications for marker-assisted breeding in goats.

Abstract Durability is one of the technical bottlenecks restricting fuel cell electric vehicle development. As a result, significant time and resources have been invested in research related to this area worldwide. Current durability research mainly focuses on the single cell and stack levels, which is quite different from the usage scenarios of actual vehicles. There is almost no research on developing durability test cycles on the fuel cell system level. This paper proposes a universal model for developing a durability test cycle for fuel cell system based on the China automotive test cycle. Large-scale comparison tests of the fuel cell systems are conducted. After 1000 h test, the output performance degradation of three mass-produced fuel cell system is 14.49%, 9.59%, and 4.21%, respectively. The test results show that the durability test cycle proposed in this paper can effectively accelerate the durability test of the fuel cell system and evaluate the durability performance of the fuel cell system. Moreover, the methodology proposed in this paper could be used in any other test cycles such as NEDC (New European Driving Cycle), WLTC (Worldwide Harmonized Light Vehicles Test Procedure), etc. And it has comprehensive application value and are significant for reducing the cost of durability testing of fuel cell systems and promoting the industrialization of fuel cell electric vehicles.

Ovarian follicle development is associated with the physiological functions of granulosa cells (GCs), including proliferation and apoptosis. The level of miR-24-3p in ovarian tissue of high-yielding Yorkshire×Landrace sows was significantly higher than that of low-yielding sows. However, the functions of miR-24-3p on GCs are unclear. In this study, using flow cytometry, 5-ethynyl-2´-de-oxyuridine (EdU) staining, and cell count, we showed that miR-24-3p promoted the proliferation of GCs increasing the proportion of cells in the S phase and upregulating the expression of cell cycle genes, moreover, miR-24-3p inhibited GC apoptosis. Mechanistically, on-line prediction, bioinformatics analysis, a luciferase reporter assay, RT-qPCR, and Western blot results showed that the target gene of miR-24-3p in proliferation and apoptosis is cyclin-dependent kinase inhibitor 1B (P27/CDKN1B). Furthermore, the effect of miR-24-3p on GC proliferation and apoptosis was attenuated by P27 overexpression. These findings suggest that miR-24-3p regulates the physiological functions of GCs.

Abstract To improve the power density of series‐connected multi‐pulse rectifiers (MPRs), the harmonic generation principle is studied and the optimization design method for main transformers is proposed. According to the topology of series‐connected 18‐pulse rectifier, its operation waveforms are analysed, and the Fourier series of the waveforms is obtained. Based on the operation waveforms and its Fourier analysis, the principle for harmonic generation of the rectifier is researched, and the phenomenon of autotransformer cannot be applied to series‐connected MPRs is researched. According to the characteristics of the transformer, its vector graphics are analysed. Based on the vector graphics, the optimal structure of the transformer with the highest power density is obtained. The results show that the premise of the normal operation of series‐connected MPRs is the potential difference between the neutral points of different secondary windings, and only isolation/semi‐isolation transformers meet the requirement; the kilovolt‐ampere (kVA) rating of the optimal isolation type transformer is 104.6% pu, and the kVA rating of the optimal semi‐isolation type transformer is about 71.23% pu.

Abstract Zinc bromine flow batteries (ZBFBs) are well suited for stationary energy storage due to their attractive features of high energy density and low cost. Nevertheless, the ZBFBs suffer from low power density and limited efficiency owing to the relatively severe polarization of the Br2/Br− redox couple. Herein, a three‐dimensional (3D) hierarchical composite electrode based on core‐shell Ni/NiO heterostructures anchored on graphite felt (Ni/NiO@GF) is designed to promote the kinetics of the Br2/Br− couple, so as to improve the power density and efficiency of the ZBFB. In this design, the highly conductive carbon felt and Ni cores provide a composite electrode with a 3D electron transporting framework to guarantee excellent electronic conductivity, while the NiO shells possess great absorption ability to Br2 and brilliant catalytic activity for the Br2/Br− redox reaction to reduce the electrochemical polarization. As a result, an enhanced ZBFB with Ni/NiO@GF electrode shows an outstanding energy efficiency of 86% at 20 mA cm−2 and can be operated at a current density of up to 160 mA cm−2 with a respectable energy efficiency of 67%. These results exhibit a promising strategy to fabricate catalytic electrodes for high‐performance ZBFBs.

Abstract Background Chronic graft-versus-host disease (cGVHD) is an immune-related disorder that is the most common complication post-allogenic hematopoietic stem cell transplant. Corticosteroids with or without calcineurin inhibitors (CNIs) remain the mainstay of cGVHD treatment for first-line therapy. However, for many patients, cGVHD symptoms cannot be effectively managed and thus require second-line therapy. Currently, there is no approved treatment for second-line cGVHD treatment in China. In this study, belumosudil, a highly selective and potent rho-associated coiled-coil-containing protein kinase-2 inhibitor demonstrated to be effective for cGVHD in the United States and other Western countries, is investigated in patients with cGVHD in China for its overall benefit–risk balance. Methods This multicenter, open-label phase II study evaluated the safety, efficacy, and pharmacokinetics of oral belumosudil 200 mg once daily in cGVHD patients who had been treated with at least one line of systemic therapy in China. The primary endpoint was overall response rate (ORR); each individual patient’s response was assessed by the investigator using the 2014 National Institutes of Health consensus criteria. Secondary endpoints were duration of response (DOR), time to response (TTR), changes in Lee Symptom Scale (LSS) score, organ response rate, corticosteroid dose change, CNI dose change, failure-free survival, time-to-next-treatment, overall survival, and safety. Results Thirty patients were enrolled in the study with a median follow-up time of 12.9 months. ORR was 73.3% (95% confidence interval: 54.1–87.7%) and all responders achieved partial response. Median DOR among responders was not reached and median TTR was 4.3 weeks (range: 3.9–48.1). Fifteen patients (50.0%) achieved clinically meaningful response in terms of reduction in LSS score by ≥ 7 points from baseline. Corticosteroid and CNI dose reductions were reported in 56.7% (17/30) and 35.0% (7/20) of patients, respectively. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity, with 11 patients (36.7%) experiencing grade ≥ 3 TEAEs. The most common grade ≥ 3 TEAE was pneumonia (n = 5, 16.7%). Conclusions Belumosudil treatment demonstrated a favorable benefit–risk balance in treating cGVHD patients who previously have had standard corticosteroid therapy in China where approved second-line setting is absent. Trial registration ClinicalTrials.gov identifier NCT04930562.

Abstract Biosynthetic enzymes evolutionarily gain novel functions, thereby expanding the structural diversity of natural products to the benefit of host organisms. Diels-Alderases (DAs), functionally unique enzymes catalysing [4 + 2] cycloaddition reactions, have received considerable research interest. However, their evolutionary mechanisms remain obscure. Here, we investigate the evolutionary origins of the intermolecular DAs in the biosynthesis of Moraceae plant-derived Diels-Alder-type secondary metabolites. Our findings suggest that these DAs have evolved from an ancestor functioning as a flavin adenine dinucleotide (FAD)-dependent oxidocyclase (OC), which catalyses the oxidative cyclisation reactions of isoprenoid-substituted phenolic compounds. Through crystal structure determination, computational calculations, and site-directed mutagenesis experiments, we identified several critical substitutions, including S348L, A357L, D389E and H418R that alter the substrate-binding mode and enable the OCs to gain intermolecular DA activity during evolution. This work provides mechanistic insights into the evolutionary rationale of DAs and paves the way for mining and engineering new DAs from other protein families.

The structure of soil pores plays a crucial role in determining the distribution and retention of particulate organic matter (POM) within soil aggregates, yet the specific effects of different straw return practices on POM stabilization through soil pore structure remain poorly understood. This study aimed to quantify and visualize soil macroaggregates POM distribution and pore structure using advanced X-ray computed tomography (CT) and image processing techniques under three straw return practices: no-tillage with straw mulching (NTS), traditional rotary tillage with straw incorporation (RTS), and deep plowing with straw incorporation (DPS) in a Vertisol. A total of 27 soil aggregates (4–6 mm) from soil depths of 0–10, 10–20, and 20–40 cm were analyzed at an 8-μm resolution. The results showed that NTS significantly increased POM content and surface area density in the 0–10 cm soil layer compared to RTS. In contrast, DPS was most effective in deeper soil layers (20–40 cm), maintaining high POM content and promoting the development of extensive and well-connected pore networks, as evidenced by significantly higher connected porosity and mean breadth density of POM. Additionally, strong positive correlations were observed between POM content, connected porosity, and pore connectivity (P < 0.05). These findings highlight the importance of selecting appropriate straw return practices to optimize POM retention and enhance soil C storage, particularly in the context of sustainable soil management in Vertisols.

Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI), with gender-specific differences in susceptibility. However, the mechanism underlying this phenomenon remains unclear. Our study reveals that the gender-specific differences in susceptibility to APAP-induced hepatotoxicity are due to differences in the gut microbiota. Through microbial multi-omics and cultivation, we observed increased gut microbiota-derived deguelin content in both women and female mice. Administration of deguelin was capable of alleviating hepatotoxicity in APAP-treated male mice, and this protective effect was associated with the inhibition of hepatocyte oxidative stress. Mechanistically, deguelin reduced the expression of thyrotropin receptor (TSHR) in hepatocytes with APAP treatment through direct interaction. Pharmacologic suppression of TSHR expression using ML224 significantly increased hepatic glutathione (GSH) in APAP-treated male mice. These findings suggest that gut microbiota-derived deguelin plays a crucial role in reducing APAP-induced hepatotoxicity in female mice, offering new insights into therapeutic strategies for DILI.

ABSTRACTEvidence showed that air pollution was associated with an increased risk of tuberculosis (TB). This study aimed to study the impact of long-term exposure to ambient particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) on the acquisition of LTBI and on the risk of subsequent active disease development among rural older adults from a multicentre cohort, which have not yet been investigated to date. A total of 4790 older adults were included in a population-based, multicentre, prospective cohort study (LATENTTB-NSTM) from 2013 to 2018. The level of long-term exposure to PM2.5 for each participant was assessed by aggregating satellite-based estimates. Logistic regression and time-varying Cox proportional hazards models with province-level random intercepts were employed to assess associations of long-term exposures to PM2.5 with the risk of LTBI and subsequent development of active TB, respectively. Out of 4790 participants, 3284 were LTBI-free at baseline, among whom 2806 completed the one-year follow-up and 127 developed newly identified LTBI. No significant associations were identified between PM2.5 and the risk of LTBI. And among 1506 participants with LTBI at baseline, 30 active TB cases were recorded during the 5-year follow-up. Particularly, an increment of 5 μg/m3 in 2-year moving averaged PM2.5 was associated with a 50.6% increased risk of active TB (HR = 1.506, 95% CI: 1.161-1.955). Long-term air pollution might be a neglected risk factor for active TB development from LTBI, especially for those living in developing or less-developed areas where the air quality is poor.

This study utilized high-throughput sequencing to investigate endophytic bacteria diversity in halophytic plants Anabasis truncate (AT) and Anabasis eriopoda (AE) from the Aral Sea region. Following sequence processing, 356 Amplicon Sequence Variants (ASVs) were discovered. The abundance and variety of endophytic bacteria were higher in AT. Bacillota, Pseudomonadota, Actinomycetota, and Bacteroidota constituted the dominant in AE, whereas Pseudomonadota, Actinomycetota, Bacteroidota, and Chloroflexota constituted the dominant in AT. Biomarkers were identified through LEFSe analysis, showing host-specific patterns. PCoA indicated distinct bacterial community structures. Phylogenetic analysis revealed diverse endophytic bacteria, including potential novel taxa. PICRUSt2 predicted diverse functions for endophytic bacteria in halophytes, indicating recruitment of beneficial bacterial taxa to adapt to extreme hypersaline conditions, including plant growth-promoting, biocontrol, and halophilic/tolerant bacteria. Moreover, the evolutionary relationship, metabolic capabilities, and plant beneficial potentials of the Bacillus swezeyi strains, previously isolated from the above two halophytes, were analyzed using comparative genomic and physiological analysis. The B. swezeyi strains displayed versatile environmental adaptability, as shown by their ability to use a wide range of carbon sources and their salt tolerances. B. swezeyi possessed a wide range of enzymatic capabilities, including but not limited to proteases, cellulases, and chitinases. Comparative genomic analysis revealed that despite some variations, they shared genetic similarities and metabolic capabilities among the B. swezeyi strains. B. swezeyi strains also displayed outstanding plant-growth-promoting and antagonistic potentials, offering potential solutions to the global food crisis. This study enhances our understanding of microbial diversity in halophytes on saline-alkali land in the West Aral Sea, shedding light on the halophyte microbiome and its collaboration with hosts in highly hypersaline environments. This study also provides a scientific basis for developing high-quality microbial fertilizers and implementing sustainable agricultural practices.

Bacteria play a crucial role in pollutant degradation, biogeochemical cycling, and energy flow within river ecosystems. However, the underlying mechanisms governing bacterial community assembly and their response to environmental factors at seasonal scales in subtropical rivers remain poorly understood. In this study, we conducted 16S rRNA gene amplicon sequencing on water samples from the Liuxi River to investigate the composition, assembly processes, and co-occurrence relationships of bacterial communities during the wet season and dry season. The results demonstrated that seasonal differences in hydrochemistry significantly influenced the composition of bacterial communities. A more heterogeneous community structure and increased alpha diversity were observed during the dry season. Water temperature emerged as the primary driver for seasonal changes in bacterial communities. Dispersal limitation predominantly governed community assembly, however, during the dry season, its contribution increased due to decreased immigration rates. Co-occurrence network analysis reveals that mutualism played a prevailing role in shaping bacterial community structure. Compared to the wet season, the network of bacterial communities exhibited higher modularity, competition, and keystone species during the dry season, resulting in a more stable community structure. Although keystone species displayed distinct seasonal variations, Proteobacteria and Actinobacteria were consistently abundant keystone species maintaining network structure in both seasons. Our findings provide insights into how bacterial communities respond to seasonal environmental changes, uncovering underlying mechanisms governing community assembly in subtropical rivers, which are crucial for the effective management and conservation of riverine ecosystems.

It remains uncertain whether causal structure prediction can improve comprehension in Chinese sentences and whether the position of the headword mediates the prediction effect. We conducted an experiment to explore the effect of causal prediction and headword position in Chinese sentence reading. Participants were asked to read sentences containing causal connectives with their eye movements recorded. In the experiment, we manipulated the causal structure of the sentence and the position of the headword. We found a promoting effect of causal structure on first-pass reading time and a hindering impact on total reading time. However, the effect was not mediated by the headword position. The results show that causal syntactic prediction facilitated early-stage processing and increased the integration cost in the late stage of Chinese sentence processing. These findings also support the constraint-based approach, which suggests an isolation between semantic and syntactic processing.

Gastric cancer (GC) remains a significant global health challenge, particularly prevalent in East Asia. Despite advancements in various treatment modalities, the prognosis for patients, especially those in advanced stages, remains poor, highlighting the need for innovative therapeutic approaches. This review explores the promising potential of diterpenes, naturally occurring compounds with robust anticancer properties, derived from diverse sources such as plants, marine organisms, and fungi. Diterpenes have shown the ability to influence reactive oxygen species (ROS) generation, ferroptosis, and autophagy, positioning them as attractive candidates for novel cancer therapies. This review explores the mechanisms of action of diterpenes and their clinical implications for the treatment of GC. Additionally, it addresses the challenges in translating these compounds from preclinical studies to clinical applications, emphasizing the need for further research to enhance their therapeutic profiles and minimize potential side effects. The discussion underscores the importance of diterpenes in future anticancer strategies, particularly in the fight against gastric cancer.

BackgroundIndividualized cortical functional networks parcellation has been reported as highly reproducible at 3.0 T. However, in view of the complexity of cortical networks and the greatly increased sensitivity provided by ultra-high field 5.0 T MRI, the parcellation consistency between different magnetic fields is unclear.PurposeTo explore the consistency and stability of individualized cortical functional networks parcellation at 3.0 T and 5.0 T MRI based on spatial and functional connectivity analysis.Materials and methodsThirty healthy young participants were enrolled. Each subject underwent resting-state fMRI at both 3.0 T and 5.0 T in a random order in less than 48 h. The individualized cortical functional networks was parcellated for each subject using a previously proposed iteration algorithm. Dice coefficient was used to evaluate the spatial consistency of parcellated networks between 3.0 T and 5.0 T. Functional connectivity (FC) consistency was evaluated using the Euclidian distance and Graph-theory metrics.ResultsA functional cortical atlas consisting of 18 networks was individually parcellated at 3.0 T and 5.0 T. The spatial consistency of these networks at 3.0 T and 5.0 T for the same subject was significantly higher than that of inter-individuals. The FC between the 18 networks acquired at 3.0 T and 5.0 T were highly consistent for the same subject. Positive cross-subject correlations in Graph-theory metrics were found between 3.0 T and 5.0 T.ConclusionIndividualized cortical functional networks at 3.0 T and 5.0 T showed consistent and stable parcellation results both spatially and functionally. The 5.0 T MR provides finer functional sub-network characteristics than that of 3.0 T.

Alcoholization is an integral part of tobacco processing and volatile compounds are key to assessing tobacco alcoholization. In this study, a total of 154 volatiles from nine categories were determined by gas chromatography-ion mobility spectrometry (GC-IMS) from four grades of tobacco, of which 114 were better identified. And then, the dynamic trends of volatile compounds with significant changes in tobacco alcoholization were analyzed. The relevant volatiles with the alcoholization indices (AIs) (R > 0.8) were screened as indicators of tobacco alcoholization. Cinnamyl isobutyrate, linolenic acid alcohol, propanoic acid-M and propanoic acid-D in all tobacco samples were highly correlated with the AIs and tended to increase during the alcoholization process. In addition, linear discriminant analysis (LDA), back-propagation neural network (BPNN) and random forest (RF) classifiers were constructed for discrimination of tobacco AIs. Three classifiers trained with a combination of 20 volatiles achieved satisfactory results with area under the curve (AUC) of 0.95 (LDA), 0.94 (BPNN) and 0.97 (RF), respectively. The RF classifier gained optimal accuracy of 100 % and 96.1 % for the training and test sets, respectively. The study confirmed that GC-IMS can be used to characterize the changes of volatile compounds in tobacco during alcoholization and combined with machine learning to achieve the determination of AIs. The results of the study may provide a new means for the tobacco industry to monitor the alcoholization process and determine the degree of alcoholization.

By analyzing the deficiencies of existing hydraulic erecting systems (HESs) control methods, this study proposes a linear time-varying model predictive control (LTV-MPC) method based on the linear extended state observer (LESO) for HESs. First, the working mechanism of HESs is methodically analyzed and the corresponding state space equations are established. Second, the LESO system is designed to estimate the current unknown real-time states. Then, the LTV-MPC is employed to evaluate and output the optimal solution of the servo voltage signal. Finally, through simulation and experiment, the effectiveness of the proposed method is confirmed and discussed. The results show that the displacement error rate of the proposed method is still lower than 0.223% under larger external disturbances, which can effectively improve the control accuracy and stability of the system compared with other methods.

Background The high metastasis rate is one of the main reasons for the poor prognosis of patients with hepatocellular carcinoma (HCC). Coagulation factor Xa (FXa) and its receptor proteinase-activated receptor-2 (PAR-2) proven to promote tumor metastasis in other forms of cancer. Here, we explore the role and mechanism of FXa in the regulation of resistance of anoikis and immune escape of HCC.Methods In vitro and in vivo experiments were conducted to explore the role of FXa in HCC metastasis and its potential mechanism. The effects of FXa inhibitor rivaroxaban on HCC immunotherapy were evaluated using intrahepatic metastasis animal models and clinical trial (No. ChiCTR20000040540). We investigated the potential of FXa inhibition as a treatment for HCC.Results FXa was highly expressed in HCC and promoted metastasis by activating PAR-2. Mechanistically, FXa-activated PAR-2 endows HCC cells with the ability of anoikis resistance to survive in the circulating blood by inhibiting the extrinsic apoptosis pathway. Furthermore, suspension stimulation-induced phosphorylation of STAT2, which promotes programmed death-ligand 1 (PD-L1) transcription and inhibits the antitumor effects of immune cells by inhibiting the infiltration of CD8+T cells in tumors and the levels of secreted cytokines. In vivo inhibition of FXa with rivaroxaban reduced HCC metastasis by decreasing PD-L1 expression and exhausting tumor-infiltrating lymphocytes. Notably, the combination of rivaroxaban and anti-programmed death-1 monoclonal antibody (anti-PD-1) programmed Death-1 monoclonal antibody (anti-PD-1) induced synergistic antitumor effects in animal models. Most importantly, rivaroxaban improved the objective response rate of patients with HCC to immune checkpoint inhibitors and prolonged overall survival time.Conclusions FXa-activated PAR-2 promotes anoikis resistance and immune escape in HCC, suggesting the potential for combining coagulation inhibitors and PD-1/PD-L1 immune checkpoint blockade to enhance the therapeutic efficacy of HCC.

IntroductionIn the invaded areas, it is believed that invasive species reduce their investment in defense due to the absence of natural enemies.MethodsBy field investigation and a series of laboratory assays, This study explored the defense strategies of invasive plants.ResultsField investigation indicated that invasive plants have a antifeedant effect on herbivorous pests, and the distribution frequency of wormholes of native plants shows a peak at a distance of 2–3 m from the invasive species. The feeding preference experiment conducted with two generalist herbivorous insects (native insect Spodoptera litura and invasive insect Spodoptera frugiperda) showed that the invasive plants have a stronger antifeedant effect than native plants. By analyzing the content of secondary metabolites in the leaves of three invasive plants (Sphagneticola trilobata, Mikania micrantha, Ipomoea cairica) and three native plants (Ipomoea nil, Paederia foetida, Polygonum chinense), the leaves of invasive plants had higher concentrations of substances associated with defenses, including total phenols, flavonoids, jasmonic acid, tannin, H2O2, and total antioxidant capacity (TAC), and lower soluble protein concentrations than native plants. After leaf damage, compared to native plants, the leaves of invasive plants showed an overall increase in substances associated with defense, except for soluble sugar.DiscussionThese results suggest that invasive plants maintain active defense strategies in invaded areas, leading to changes in the distribution patterns of herbivorous insects in a manner that facilitates invasion.